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https://www.readbyqxmd.com/read/28087538/bcap-inhibits-proliferation-and-differentiation-of-myeloid-progenitors-in-the-steady-state-and-during-demand-situations
#1
Jeffrey M Duggan, Matthew B Buechler, Rebecca M Olson, Tobias M Hohl, Jessica A Hamerman
B cell adaptor for PI3-kinase (BCAP) is a signaling adaptor expressed in mature hematopoietic cells including monocytes and neutrophils. Here we investigated the role of BCAP in the homeostasis and development of these myeloid lineages. BCAP(-/-) mice had more bone marrow (BM) monocytes than WT mice, and in mixed WT:BCAP(-/-) BM chimeras, monocytes and neutrophils skewed towards BCAP(-/-) origin, showing a competitive advantage for BCAP(-/-) myeloid cells. BCAP was expressed in bone marrow hematopoietic progenitors, including LSK (Lineage(-)Sca1(+)cKit(+)), CMP (Common Myeloid Progenitor) and GMP (Granulocyte/Macrophage Progenitor) cells...
January 13, 2017: Blood
https://www.readbyqxmd.com/read/28087353/thiolated-polymers-as-mucoadhesive-drug-delivery-systems
#2
REVIEW
Sarah Duggan, Wayne Cummins, Orla O' Donovan, Helen Hughes, Eleanor Owens
Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug...
January 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28079579/detailed-2-dimensional-and-3-dimensional-transesophageal-evaluation-of-the-aortic-root-and-aortic-valve-in-complex-type-a-dissections
#3
J Kirk Edwards, Bradley G Leshnower, Michael Duggan, Kathryn E Glas
No abstract text is available yet for this article.
January 11, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28076022/renal-papillary-and-calyceal-lesions-at-ct-urography-genitourinary-imaging
#4
Satomi Kawamoto, Peter Duggan, Sheila Sheth, Hiroshi Miyamoto, Zubair N Kazi, Elliot K Fishman
No abstract text is available yet for this article.
January 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28074255/bortezomib-containing-regimens-bcr-for-the-treatment-of-non-transplant-eligible-multiple-myeloma
#5
Victor H Jimenez-Zepeda, Peter Duggan, Paola Neri, Jason Tay, Nizar J Bahlis
In multiple myeloma (MM) patients ineligible for transplant, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor with anti-myeloma effects, have been reported. We aimed to evaluate the impact of different bortezomib-containing regimens (BCR) for the treatment of transplant-ineligible MM. All- consecutive patients treated with BCR at our institution from 01/05 to 02/16 were evaluated. With a median of 6 cycles, an overall response rate of 95...
January 10, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28072390/a-molecular-portrait-of-maternal-sepsis-from-byzantine-troy
#6
Alison M Devault, Tatum D Mortimer, Andrew Kitchen, Henrike Kiesewetter, Jacob M Enk, G Brian Golding, John Southon, Melanie Kuch, Ana T Duggan, William Aylward, Shea N Gardner, Jonathan E Allen, Andrew M King, Gerard Wright, Makoto Kuroda, Kengo Kato, Derek Eg Briggs, Gino Fornaciari, Edward C Holmes, Hendrik N Poinar, Caitlin S Pepperell
Pregnancy complications are poorly represented in the archeological record, despite their importance in contemporary and ancient societies. While excavating a Byzantine cemetery in Troy, we discovered calcified abscesses among a woman's remains. Scanning electron microscopy of the tissue revealed 'ghost cells', resulting from dystrophic calcification, which preserved ancient maternal, fetal and bacterial DNA of a severe infection, likely chorioamnionitis. Gardnerella vaginalis and Staphylococcus saprophyticus dominated the abscesses...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28031342/transcriptional-classification-and-functional-characterization-of-human-airway-macrophage-and-dendritic-cell-subsets
#7
Vineet I Patel, J Leland Booth, Elizabeth S Duggan, Steven Cate, Vicky L White, David Hutchings, Susan Kovats, Dennis M Burian, Mikhail Dozmorov, Jordan P Metcalf
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR(+)) were consistently observed...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28028675/glottic-impersonation
#8
George Kovacs, Laura V Duggan, Peter G Brindley
No abstract text is available yet for this article.
December 27, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28028213/programming-function-into-mechanical-forms-by-directed-assembly-of-silk-bulk-materials
#9
Benedetto Marelli, Nereus Patel, Thomas Duggan, Giovanni Perotto, Elijah Shirman, Chunmei Li, David L Kaplan, Fiorenzo G Omenetto
We report simple, water-based fabrication methods based on protein self-assembly to generate 3D silk fibroin bulk materials that can be easily hybridized with water-soluble molecules to obtain multiple solid formats with predesigned functions. Controlling self-assembly leads to robust, machinable formats that exhibit thermoplastic behavior consenting material reshaping at the nanoscale, microscale, and macroscale. We illustrate the versatility of the approach by realizing demonstrator devices where large silk monoliths can be generated, polished, and reshaped into functional mechanical components that can be nanopatterned, embed optical function, heated on demand in response to infrared light, or can visualize mechanical failure through colorimetric chemistries embedded in the assembled (bulk) protein matrix...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28002958/discovery-of-n-bis-4-methoxyphenyl-methyl-4-hydroxy-2-pyridazin-3-yl-pyrimidine-5-carboxamide-mk-8617-an-orally-active-pan-inhibitor-of-hypoxia-inducible-factor-prolyl-hydroxylase-1-3-hif-phd1-3-for-the-treatment-of-anemia
#10
John S Debenham, Christina Madsen-Duggan, Matthew J Clements, Thomas F Walsh, Jeffrey T Kuethe, Mikhail Reibarkh, Scott P Salowe, Lisa M Sonatore, Richard Hajdu, James A Milligan, Denise M Visco, Dan Zhou, Russell B Lingham, Dominique Stickens, Julie A DeMartino, Xinchun Tong, Michael Wolff, Jianmei Pang, Randy R Miller, Edward C Sherer, Jeffrey J Hale
The discovery of novel 4-hydroxy-2-(heterocyclic)pyrimidine-5-carboxamide inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD) is described. These are potent, selective, orally bioavailable across several species, and active in stimulating erythropoiesis. Mouse and rat studies showed hematological changes with elevations of plasma EPO and circulating reticulocytes following single oral dose administration, while 4-week q.d. po administration in rat elevated hemoglobin levels. A major focus of the optimization process was to decrease the long half-life observed in higher species with early compounds...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27989050/seroprevalence-of-q-fever-in-patients-undergoing-heart-valve-replacement-surgery
#11
Owen Seddon, Reza Ashrafi, Jacqueline Duggan, Rhianydd Rees, Christine Tan, John Williams, Gail Carson, Brendan Healy
BACKGROUND: Q fever, caused by the rickettsia Coxiella burnetii, is a worldwide zoonotic disease with both acute and chronic manifestations. Endocarditis is the principal chronic manifestation. Q fever can easily be mistaken for degenerative valve disease due to its indolent presentation, the fastidious nature of the organism (routine cultures are negative), and the absence of a typical echocardiographic and macroscopic appearance for endocarditis. Prosthetic valve failure, with associated morbidity and mortality, have been described following unrecognized infections...
May 2016: Journal of Heart Valve Disease
https://www.readbyqxmd.com/read/27988834/selexipag-a-review-in-pulmonary-arterial-hypertension
#12
Sean T Duggan, Susan J Keam, Celeste B Burness
Selexipag (Uptravi(®)) is an orally active, first-in-class, selective prostacyclin IP receptor agonist. Selexipag was approved recently in the EU for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II or III as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor or as monotherapy in patients who are not candidates for these therapies, and in the USA for the treatment of PAH (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH...
February 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/27986469/a-systematic-review-of-the-psychobiological-burden-of-informal-caregiving-for-patients-with-dementia-focus-on-cognitive-and-biological-markers-of-chronic-stress
#13
REVIEW
Andrew P Allen, Eileen A Curran, Áine Duggan, John F Cryan, Aoife Ní Chorcoráin, Timothy G Dinan, D William Molloy, Patricia M Kearney, Gerard Clarke
As the physiological impact of chronic stress is difficult to study in humans, naturalistic stressors are invaluable sources of information in this area. This review systematically evaluates the research literature examining biomarkers of chronic stress, including neurocognition, in informal dementia caregivers. We identified 151 papers for inclusion in the final review, including papers examining differences between caregivers and controls as well as interventions aimed at counteracting the biological burden of chronic caregiving stress...
December 13, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27940225/migration-and-interaction-tracking-for-quantitative-analysis-of-phagocyte-pathogen-confrontation-assays
#14
Susanne Brandes, Stefanie Dietrich, Kerstin Hünniger, Oliver Kurzai, Marc Thilo Figge
Invasive fungal infections are emerging as a significant health risk for humans. The innate immune system is the first line of defense against invading micro-organisms and involves the recruitment of phagocytes, which engulf and kill pathogens, to the site of infection. To gain a quantitative understanding of the interplay between phagocytes and fungal pathogens, live-cell imaging is a modern approach to monitor the dynamic process of phagocytosis in time and space. However, this requires the processing of large amounts of video data that is tedious to be performed manually...
November 25, 2016: Medical Image Analysis
https://www.readbyqxmd.com/read/27939314/17-th-century-variola-virus-reveals-the-recent-history-of-smallpox
#15
Ana T Duggan, Maria F Perdomo, Dario Piombino-Mascali, Stephanie Marciniak, Debi Poinar, Matthew V Emery, Jan P Buchmann, Sebastian Duchêne, Rimantas Jankauskas, Margaret Humphreys, G Brian Golding, John Southon, Alison Devault, Jean-Marie Rouillard, Jason W Sahl, Olivier Dutour, Klaus Hedman, Antti Sajantila, Geoffrey L Smith, Edward C Holmes, Hendrik N Poinar
Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone...
December 19, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27939174/challenges-in-the-development-of-an-m4-pam-in-vivo-tool-compound-the-discovery-of-vu0467154-and-unexpected-dmpk-profiles-of-close-analogs
#16
Michael R Wood, Meredith J Noetzel, Michael S Poslusney, Bruce J Melancon, James C Tarr, Atin Lamsal, Sichen Chang, Vincent B Luscombe, Rebecca L Weiner, Hyekyung P Cho, Michael Bubser, Carrie K Jones, Colleen M Niswender, Michael W Wood, Darren W Engers, Nicholas J Brandon, Mark E Duggan, P Jeffrey Conn, Thomas M Bridges, Craig W Lindsley
This letter describes the chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core, developed via iterative parallel synthesis, and culminating in the highly utilized rodent in vivo tool compound, VU0467154 (5). This is the first report of the optimization campaign (SAR and DMPK profiling) that led to the discovery of VU0467154, and details all of the challenges faced in allosteric modulator programs (steep SAR, species differences in PAM pharmacology and subtle structural changes affecting CNS penetration)...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27919781/budgie-in-the-mirror-an-exploratory-analysis-of-social-behaviors-and-mirror-use-in-the-budgerigar-melopsittacus-undulatus
#17
Daniel P Buckley, Michael R Duggan, Matthew J Anderson
Despite their prevalent use amongst avian species, particularly in Budgerigars, the relationship between mirror use and social behaviors is in need of elucidation. After establishing social behavior measures (e.g., agonistic and pair-bond data) in a colony of Budgerigars, mirrors were introduced and subsequent use was documented. Results illustrated a significant relationship between mirror use and pair-bonds, such that mirror use increased with increasing pair-bond strength. The authors posit that individual differences in gregariousness may best account for the obtained results, with certain birds seeking more social stimulation than others, whether it be from a pair-bond or from its own reflected mirror image...
December 2, 2016: Behavioural Processes
https://www.readbyqxmd.com/read/27916415/hospital-discharges-and-patient-activity-associated-with-chronic-pancreatitis-in-ireland-2009-2013
#18
Hazel M Ní Chonchubhair, Yasir Bashir, David McNaughton, Joseph M Barry, Sinead N Duggan, Kevin C Conlon
OBJECTIVE: To investigate trends in acute public hospital patient discharges in Ireland, to analyse hospital discharge activity for geographical variations, aetiological differences, and to estimate a national prevalence for chronic pancreatitis. METHOD: We performed a nationwide retrospective study of all in-patient discharges from acute public hospitals in Ireland, participating in the Hospital In-Patient Enquiry (HIPE) reporting system. We searched for International Classification of Disease, Tenth Revision, Australian Modification (ICD-10-AM) codes K86...
November 25, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/27885604/assays-to-study-the-interaction-of-campylobacter-jejuni-with-the-mucosal-surface
#19
Marguerite Clyne, Gina Duggan, Ciara Dunne, Brendan Dolan, Luis Alverez, Billy Bourke
Mucosal colonization and overcoming the mucosal barrier are essential steps in the establishment of infection by Campylobacter jejuni. The interaction between C. jejuni and host cells, including binding and invasion, is thought to be the key virulence factor important for pathogenesis of C. jejuni infections in animals or humans. The intestinal mucosal barrier is composed of a polarized epithelium covered by a thick adherent mucus gel layer. There is a requirement for cell culture assays of infection to accurately represent the in vivo mucosal surface...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27885602/methods-to-assess-the-direct-interaction-of-c-jejuni-with-mucins
#20
Marguerite Clyne, Gina Duggan, Julie Naughton, Billy Bourke
Studies of the interaction of bacteria with mucus-secreting cells can be complemented at a more mechanistic level by exploring the interaction of bacteria with purified mucins. Here we describe a far Western blotting approach to show how C. jejuni proteins separated by SDS PAGE and transferred to a membrane or slot blotted directly onto a membrane can be probed using biotinylated mucin. In addition we describe the use of novel mucin microarrays to assess bacterial interactions with mucins in a high-throughput manner...
2017: Methods in Molecular Biology
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